14 DAY TRIAL // A breakthrough in understanding sporadic breast cancers has been made by researchers at the University of Pittsburgh School of Medicine, Magee-Womens Hospital of UPMC and the University of Pittsburgh Cancer Institute.
The team found out that when breast cancer is not inherited through certain genes and it occurs sporadically, it likely starts with flaws of DNA repair mechanisms, that tolerate environmentally triggered mutations to accumulate.
This means that the strong chemotherapy drugs that target DNA and are used in later-stage cancers, could be very effective in treating the earliest breast tumors.
One of the reasons this new research has focused on familial breast cancers is because the predisposing genes are well-characterized and women at risk can be identified, Jean J. Latimer, PhD, assistant professor of obstetrics, gynecology and reproductive sciences at Pitt’s School of Medicine, said.
But the fact is that this type of cancer only represents 15% of the 190,000 breast cancers diagnosed every year in the US.
Also, this research use the available cell lines derived from late-stage tumors, but most newly diagnosed tumors are stage I.
In the team's previous work, they found that breast tissue does dot repair everyday damage to DNA, as other tissues, like skin, do.
For example, UV light can cause mutations but inside the skin there is a complex system of nucleotide excision repair (NER) proteins that analyzes the DNA strands to find problems and start repair processes.
This system works for many environmental carcinogens, tobacco smoke included, but inside breast tissue, even if it is perfectly healthy, “this system is only about one-fifth as effective as it is in skin,” Dr. Latimer explained.
“This deficiency could set the stage for sporadic cancer development, with the risk increasing with age as DNA damage accumulates.”
So, for this study, the scientists grew and evaluated 19 sporadic, stage I breast tumors placed into culture directly from surgeries, in order to test their NER pathways.
In all 19 cases, there was a flaw in repair ability compared to disease-free breast tissue, and according to Dr Latimer, “that is a remarkably consistent feature for cancers that might otherwise seem random in their genesis.
“We rarely see a universal rule when it comes to breast cancer, but then until now, we have rarely studied stage I disease.”
Some chemotherapy drugs work especially well on cells that exhibit reduced DNA repair, but they are normally given in later-stage disease. The new findings suggest, if given in early stages, these approaches could be more effective.
Dr. Latimer explained that the “team is able to grow stage I breast cancer cells – before they have spread to adjacent tissues and lymph nodes – allowing us to examine the mechanisms that underlie cancer development in people who didn’t inherit a faulty gene.
“The advent of innovative tissue engineering techniques has finally made it possible for us to culture these cells to determine what has gone wrong.”
This new research was funded by the National Institutes of Health, the US Department of Defense, the Pennsylvania Department of Health, the Komen for the Cure Awards, and the American Cancer Society, and the findings were reported this week in the early online edition of the Proceedings of the National Academy of Sciences.